This research will explore the role of gonadal and adrenal steroid hormones in the development and function of the magnocellular neurons of the hypothalamus. These neuro-secretory cells make and release the hormones of the posterior pituitary, oxytocin and vasopressin. Knowledge of the factors controlling their differentiation and activity is central to an understanding of the role of neuroendocrine systems in maintaining homeostasis in the organism. In addition, these biochemically and functionally identified neurons provide an excellent model system for studying the mechanisms of steroid hormone action in the brain. These studies will employ transplantation of embryonic rat hypothalamus to the choroidal pia overlying the superior colliculus in adult rat (host) brains. This system offers several unique advantages. First, the hormonal environment of the developing hypothalamus can be controlled to an extent impossible in utero. Second, magnocellular neurons in transplants are deprived of their extrahypothalamic afferents. Thus the role of these inputs can be studied by measuring the metabolic response of transplanted magnocellular neurons to changes in the hormonal status of the host. Third, the magnocellular neurons of the host brain provide contemporaneous controls for the immunocytochemical and autoradiographic procedures and hormonal manipulations in these experiments. Initial studies revealed that development of transplanted hypothalamus in hosts without gonads or adrenal glands markedly reduced the number of immunocytochemically identified magnocellular neurons in the transplant. Specific aims of the proposed research include: (1) determining which steroids mediate this effect and whether it is reversible or has a critical period during development; (2) testing whether specific intracellular steroid receptors mediate this effect; (3) investigating the role of steroids in development of two additional immunocytochemically identified cell types, parvicellular vasopressin cells and fibrous astrocytes; (4) determining the ability of transplanted magnocellular neurons to respond to acute changes in the host hormonal status; (5) exploring the role of gestational age and the presence of the fetal neurohypophysis in development of transplanted magnocellular neurons.